Data-driven subtypes of mixed semantic-logopenic primary progressive aphasia: Linguistic features, biomarker profiles and brain metabolic patterns

Salvatore Mazzeo; Carmen Morinelli; Cristina Polito; Giulia Giacomucci; Valentina Moschini; Assunta Ingannato; Juri Balestrini; Daniele Frigerio; Filippo Emiliani; Giulia Galdo; Chiara Crucitti; Diletta Piazzesi; Silvia Bagnoli; Sonia Padiglioni; Valentina Berti; Sandro Sorbi; Benedetta Nacmias; Valentina Bessi

doi:10.1016/j.jns.2024.122998

Data-driven subtypes of mixed semantic-logopenic primary progressive aphasia: Linguistic features, biomarker profiles and brain metabolic patterns

J Neurol Sci. 2024 Apr 6:460:122998. doi: 10.1016/j.jns.2024.122998. Online ahead of print.

Authors

Salvatore Mazzeo¹, Carmen Morinelli², Cristina Polito³, Giulia Giacomucci⁴, Valentina Moschini², Assunta Ingannato⁴, Juri Balestrini⁴, Daniele Frigerio⁴, Filippo Emiliani⁴, Giulia Galdo⁴, Chiara Crucitti⁴, Diletta Piazzesi², Silvia Bagnoli⁴, Sonia Padiglioni⁵, Valentina Berti⁶, Sandro Sorbi⁷, Benedetta Nacmias⁷, Valentina Bessi⁸

Affiliations

¹ Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Italy; Research and Innovation Centre for Dementia-CRIDEM, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy; Vita-Salute San Raffaele University, Milan, Italy; IRCCS Policlinico San Donato, San Donato Milanese, Italy.
² Research and Innovation Centre for Dementia-CRIDEM, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.
³ IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy.
⁴ Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Italy.
⁵ Research and Innovation Centre for Dementia-CRIDEM, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy; Regional Referral Centre for Relational Criticalities, 50139 Tuscany Region, Italy.
⁶ Department of Biomedical, Experimental and Clinical Sciences "Mario Serio", University of Florence, Italy.
⁷ Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Italy; IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy.
⁸ Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Italy; Research and Innovation Centre for Dementia-CRIDEM, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy. Electronic address: valentina.bessi@unifi.it.

PMID: 38615405
DOI: 10.1016/j.jns.2024.122998

Abstract

Mixed primary progressive aphasia (mPPA) accounts for a substantial proportion of primary progressive aphasia (PPA) cases. However, the lack of a standardised definition of this condition has resulted in misclassification of PPA cases. In this study, we enrolled 55 patients diagnosed with PPA, comprising 12 semantic variant (svPPA), 23 logopenic variant (lvPPA), and 20 mPPA cases with linguistic characteristics consistent with both svPPA and lvPPA (s/lvPPA). All patients underwent language assessments, evaluation of Alzheimer's disease biomarkers (via cerebrospinal fluid analysis or Amyloid-PET), and ¹⁸F-FDG-PET brain scans. An agglomerative hierarchical clustering (AHC) analysis based on linguistic characteristics revealed two distinct clusters within the s/lvPPA group: cluster k1 (n = 10) displayed an AD-like biomarker profile, with lower levels of Aβ₄₂ and Aβ₄₂/Aβ₄₀ ratio, along with higher levels of t-tau and p-tau compared to cluster k2 (n = 10). Interestingly, k1 exhibited linguistic features that were similar to those of svPPA. Both clusters exhibited extensive temporoparietal hypometabolism. These findings support the hypothesis that a subgroup of s/lvPPA may represent a clinical manifestation of AD-related PPA.

Keywords: Alzheimer's disease; Biomarkers; Cluster analysis; Frontotemporal dementia; Primary progressive aphasia; Semantic dementia.